The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics

• Published in: Angewandte Chemie 2016-01, Vol.128 (3), p.962-966
• Main Authors: O'Banion, Colin P., Nguyen, Luong T., Wang, Qunzhao, Priestman, Melanie A., Holly, Stephen P., Parise, Leslie V., Lawrence, David S.
• Format: Article
• Language: eng ; ger
• Subjects: Anchors; Backbone; Biological effects; Chemistry; Clotting; Degradation; Environments; Erythrocytes; Gezielter Transport; Hormones; Launching pads; Light effects; Lipids; Peptide; Peptides; Peptidwirkstoffe; Permeability; Photochemie; Plasma; Protease; Protective; Proteinase; Proteolyse; Reservoirs; Shields
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201508767

Although peptide‐based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light‐triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease‐resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light‐triggered peptide release from erythrocytes. We have shown that a cell‐permeable peptide, a hormone (melanocyte stimulating hormone), and a blood‐clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect. Sicherer Hafen: Ein Anheften an die Plasmamembran von Erythrozyten lässt sich nutzen, um therapeutische Peptide vor Serumproteasen zu schützen. Eine photospaltbare Einheit ist zwischen dem Lipidanker und dem Peptidrückgrat eingefügt, was eine photoinduzierte Freisetzung ermöglicht.